ECF varies when either [HCO3 −] or PCO2 are altered. As already noted, disturbances of acid-base balance that result from a change in [HCO3 −] of ECF are termed metabolic acid-base disorders, whereas those resulting from a change in PCO2 are termed respiratory acid-base disorders. The kidneys are primarily responsible for regulating [HCO3 −], whereas the lungs regulate PCO2.
When an acid-base disturbance develops, the body uses several mechanisms to defend against the change in ECF pH. These defense mechanisms do not correct the acid-base disturbance but merely minimize the change in pH imposed by the disturbance. Restoration of the blood pH to its normal value requires correction of the underlying process or processes that produced the acid-base disorder. The body has three general mechanisms to defend against changes in body fluid pH produced by acid-base disturbances: (1) extracellular and intracellular buffering, (2) adjustments in blood PCO2 via alterations in the ventilatory rate of the lungs, and (3) adjustments in RNAE.
The first line of defense against acid-base disorders is extracellular and intracellular buffering. The response of the extracellular buffers is virtually instantaneous, whereas the response to intracellular buffering is slower and can take several minutes.
Metabolic disorders that result from addition of nonvolatile acid or alkali to body fluids are buffered in both the extracellular and intracellular compartments. The HCO3 − buffer system is the principal ECF buffer. When nonvolatile acid is added to body fluids (or alkali is lost from the body), HCO3 − is consumed during the process of neutralizing the acid load, and the [HCO3 −] of ECF is reduced. Conversely, when nonvolatile alkali is added to body fluids (or acid is lost from the body), H+ is consumed, causing more HCO3 − to be produced from the dissociation of H2CO3. Consequently, [HCO3 −] increases.
Although the HCO3 − buffer system is the principal ECF buffer, Pi and plasma proteins provide additional extracellular buffering. The combined action of the buffering processes for HCO3 − , Pi, and plasma protein accounts for approximately 50% of the buffering of a nonvolatile acid load and 70% of a nonvolatile alkali load. The remainder of the buffering under these two conditions occurs intracellularly. Intracellular buffering involves movement of H+ into cells (during buffering of nonvolatile acid) or movement of H+ out of cells (during buffering of nonvolatile alkali). H+ is titrated inside the cell by HCO3 − , Pi, and the histidine groups on proteins.
Bone represents an additional source of extracellular buffering. However, with acidosis, buffering by bone results in its demineralization.
When respiratory acid-base disorders occur, the pH of body fluid changes as a result of alterations in PCO2. Virtually all buffering in respiratory acid-base disorders occurs intracellularly. When PCO2 rises (respiratory acidosis), CO2 moves into the cell, where it combines with H2O to form H2CO3. H2CO3 then dissociates to H+ and HCO3 − . Some of the H+ is buffered by cellular proteins, and HCO3 − exits the cell and raises the ECF [HCO3 −]. This process is reversed when PCO2 is reduced (respiratory alkalosis). Under this condition the hydration reaction (H2O + CO2 ↔ H2CO3) is shifted to the left by the decrease in PCO2. As a result the dissociation reaction (H2CO3 ↔ H++ HCO3 −) also shifts to the left, thereby reducing the ECF [HCO3 −].
The lungs are the second line of defense against acid-base disorders. As indicated by the Henderson-Hasselbalch equation (see
Eq. 37.2 ), changes in PCO2 alter the blood pH: a rise decreases the pH, and a reduction increases the pH.